Systemic sclerosis (SSc) is a multisystem disorder characterized by skin thickening, with a peak incidence in women aged 35-64. The etiology remains largely unknown, involving both environmental and genetic factors, and presents as limited or diffuse forms with varied organ involvement. Treatment focuses on managing symptoms and complications across affected systems, including pulmonary, renal, and gastrointestinal manifestations.

1. Systemic Sclerosis (SSc
W. P. Rivindu H. Wickramanayake
Group no. 04a
5th Year 2nd Semester – 2019 October
Tbilisi State Medical University, Georgia

2. Telangiectasias affecting the face: They are pronounced
and numerous, especially in the atrophic phase of the disease.
Radical furrowing around the mouth is also characteristic in the
later stage of the disease.
• Multisystem disorder
• Unknown etiology
• Thickening of skin caused by
accumulation of connective tissue
(collagen types I and III)
• Involvement of visceral organs
• Peak age range: 35-64
• Younger age in women and with
diffuse disease.
• Female : Male = 3:1
• 8:1 in child bearing years
• Incidence: 20/million per year in US
• Prevalence: 240/million in US.

3.  Unknown / Idiopathic
 Chemical radiation exposure
 Environmental Exposures
• Silica exposure in men conferred increased risk
• Silicone breast implants: no definite risk identified
• Aniline laced Contaminated rapseed oil in Spain
• Vinyl chloride exposure increased risk of SSc like disorder: Eosinophilic Fasciitis
• bleomycin
• L-tryptophan: Eosinophilia Myalgia syndrome
 Genetic Factors
• Familial Clustering: 1.5-2.5% of those with 1st degree relative – Choctow
Native Americans: prevalence 4720/million.
• HLA-haplotypes: there are higher risk haplotypes in certain populations
Etiology

4.  The CD4 cells(lymphocytes) reacted against some antigens
in the body resulting to accumulation of the lymphocytes and
thus cytokines are released causing vascular cell injury.
 These damaged endothelium produces less vasodilators and
more vasoconstrictors which causes decrease oxygen supply
and resulting in tissue hypoxia.
 Also tissue growth factor is released by the damaged tissue
thus causing activation of fibroblast resulting in the fibroblast
to start producing collagen and extracellular proteins in
excess.
Pathogenesis

12.  Limited Scleroderma
• Skin thickening is distal to elbows and knees, not involving trunk
• Can involve perioral skin thickening (pursing of lips)
• Less organ involvement
• Seen in CREST syndrome
• Isolated pulmonary hypertension can occur
 Diffuse Scleroderma
• Skin thickening proximal to elbows and knees, involving the trunk
• More likely to have organ involvement
• Pulmonary fibrosis and Renal Crisis are more common.
Main Forms of Systemic Sclerosis

13.  More gradual process
• Can have Raynaud’s for years (even up to decade)
 Skin involvement distal to elbows and knees
• Often with perioral involvement (pursing of lips)
 Capillaroscopy
• with dilated capillary loops but without dropout.
 Less organ involvement
• though 10-15% with isolated pulmonary hypertension.
• Renal involvement is rare.
 Anti-centromere Ab in 70-80%
Limited Scleroderma

16. Nailfold Capillaroscopy

18.  More Rapid Process
• Often with onset of skin thickening within a year of Raynaud’s
symptoms
 Skin involvement proximal to elbows and knees
• Often can involve the trunk
 Capillaroscopy reveals dropout
• With capillary dilatation and dropout.
 Early organ involvement
• Renal, interstitial lung disease, myocardial, diffuse gastrointestinal
– often within the first 3 years.
 Antibodies
• Anti-Scl-70, anti-RNA Polymerase III.
Diffuse Scleroderma

19. • Skin
• Musculoskeletal
• Pulmonary
• Renal
• Gastrointestinal
• Cardiac
Organs Involved

20.  Early stages:
• Perivascular infiltrate which are primarily T cells.
• Skin swelling which eventually becomes skin thickening.
• Involves the hands and/or feet (distal).
 Late Stages:
• Finger-like projections of collagen extend from the dermis to
the subcutaneous tissue to anchor skin deeper.
• Skin becomes firm, thick and tight.
• Skin thickening moves proximally.
• Fibroblasts and collagen deposition.
• Hair and wrinkles overlying area of skin thickening disappears.
Skin Involvement

21.  May regress on its own over years
• reverse pattern (ie, starting with regression of skin
thickening in the trunk, then proximal extremities, then
more distal).
 Digital Ulcers:
• on extensor surface of PIP’s and elbows; may become
secondarily infected.
 Digital ischemia:
• with pits in the distal aspect of the digits related to
prolonged Raynaud’s.
 Thinning of the lips, beak-like nose.

23.  Arthritis
• in > 50% with swelling,
stiffness, and pain in the joints of the
hands.
 Carpal Tunnel Syndrome.
 Contractures
• related to skin thickening.
 Polymyositis
• may occur as part of mixed
connective tissue disease or overlap.
Musculoskeletal
 Leading cause of death
• since we are better at control
of renal disease.
 Symptoms:
• exertional dyspnea
 Types of lung Involvement:
• Interstitial lung disease.
• Isolated pulmonary
hypertension.
Pulmonary

24.  Inflammatory phase
• with ground glass opacities and linear infiltrates
• lower 2/3 of the lung fields on CT scan.
 Fibrosis:
• Late phase with honeycombing.
 Diagnosis
– Pulmonary function tests
• restrictive pattern with low FVC, low residual volume, low DLCO.
– High Resolution CT Scan
– BAL: often not required
– Lung biopsy: often not required
 ILD is most commonly associated with diffuse
scleroderma. • Anti-Scl-70
Interstitial Lung Disease

25.  Symptoms: • exertional dyspnea.
 Frequency :- 10-15% of patients with SSc
 Definition:
• Mean PA blood pressure >25mmHg at rest or
>30mmHg with exercise on right heart catheterization.
• Estimated systolic pulmonary artery pressure of
>35mmHg on Echocardiogram
 Pathogenesis
• Intimal fibrosis and medial hypertrophy of the
pulmonary arterioles and arteries.
Pulmonary HTN

26.  Pneumonia:
• due to aspiration secondary to
GERD; skin thickening of chest
may reduce effectiveness of cough.
 Alveolar carcinoma:
increased incidence
 Bronchogenic carcinoma:
increased incidence.
Other Pulmonary Associations

27.  Pericardial Effusion
– symptomatic pericarditis in 20%
 Microvascular CAD:
– recurrent vasospasm of coronary arteries
– Necrosis
– patchy myocardial fibrosis; leads to diastolic > systolic
dysfunction.
 Myocarditis
– Inflammation which leads to fibrosis
 Arrhythmias and conduction abnormalities
– Fibrosis of cardiac conduction system.
– AV conduction defects and arrhythmias.
Cardiac Manifestations
• Forms of cardiac involvement

29.  Scleroderma Renal Crisis
• Abruptly developing severe hypertension
– Rise in SBP by > 30 mmHg, DBP by > 20 mm Hg
• One of the following:
– Increase in serum creatinine by 50% over baseline or creatinine >
120% of upper limit.
– Proteinuria > 2+ by dipstick.
– Hematuria > 2+ by dipstick or > 10 RBC/HPF
– Thrombocytopenia < 100
– Hemolysis (schisctocytes, low platelets, increased reticulocyte count).
• Can cause headache, encephalopathy, seizures, LV failure.
• 90% with blood pressure > 150/90.
• Can occur also with lower blood pressures < 140/90 and this confers
worse prognosis.
Renal Manifestations of SSc

31. Scleroderma Renal Crisis
Risk Factors for Renal Crisis
• Rapidly progressive skin thickening
within the first 2-3 years.
• Steroid use (prednisone > 15 mg)
• Anti-polymerase III Ab.
• Pericardial Effusion.
Treatment of Scleroderma Renal Crisis
• Medical Emergency: generally with admission.
• Initiation of ACE inhibitors such as captopril;
lifelong treatment with ACE inhibitors.
• Dose escalation of captopril.
• ACE-inhibitors do not prevent SRC.

32. • Improved overall with ACE-
inhibitors.
• Even with ACE-inhibitors 20-
50% will progress to ESRD.
• Among patients who required
dialysis during the acute phase,
an appreciable proportion (40-
50%) will be able to
discontinue dialysis.
Renal Crisis - Prognosis

33.  Esophageal dysmotility: in up to 90%.
• Pathophysiology:
– reduced tone of gastroesophageal sphincter and distal dilatation of the esophagus.
– Lamina propia and submucosal tissue with Inflammatory changes and increased
collagen on pathology.
• Symptoms – Dysphagia, GERD; many asymptomatic.
• Diagnosis: – Esophageal manometry, Esophagram, CT scan.
• Treatment: – Proton Pump Inhibitors
– Elevation of head of the bed.
• Complications: – Barret’s Esophagus.
 Colon Involvement:
• Can cause symptoms of constipation due to decreased peristalsis.
• Fecal incontinence can occur due to alterations of internal and external
sphincter.
Gastrointestinal Manifestations

34.  Gastric Involvement:
• Symptoms: Early satiety.
• Diagnosis: Nuclear Gastric Emptying Test.
• Treatment: promotility agents
• Watermelon Stomach: dilated vessel which can cause
bleeding.
 Small Intestinal involvement
• Symptoms: distension, pain, bloating, steatorrhea
• nutritional deficiencies secondary to bacterial overgrowth. »
Vitamin B6/B12/folate/25-OH Vit D, low albumin
• Diagnosis:
– glucose hydrogen breath test
– Low D-xylose absorption test
– small bowel aspiration (only if resistance to rotating
antibiotics)
• Treatment: Rotating antibiotics, Reglan, Erythromycin

35. SSc Autoantibodies

36.  Depends on clinical manifestations
 Aggressive disease versus stable disease
 Reversible inflammation vs Vasoconstriction.
 Organ Involvement
 Treatment is directed at organ involved.
SSc Treatment
 Calcium Channel Blockers: nifedipine
 Nitroglycerin patches
 Sildenafil (Viagra) (but not in combination with nitroglycerine)
– usually for refractory Raynaud’s.
 Parental vasodilators (iloprost)
– for severe disease with impending digital ischemia.
Raynaud’s

37.  GERD - Proton pump inhibitor.
 Delayed Gastric Emptying and
peristalis disorders
- Supportive
- Promotilants are sometimes used.
 Interstitial Lung Disease: with
active inflammation
- Mycophenolate
- Azithioprine
- Cytoxan - IV
- plus lower dose of steroids if RNA
Poly III neg (ie 10 mg daily); avoid
steroids if RNA Poly III positive.
 Pulmonary Hypertension
- Vasodilators: bosentan,
sildenafil, epoprostenol,
treprostinil, iloprost.
- Lung Heart Transplant
 Polymyositis overlap or MCTD
- Similarly to myositis alone with
methotrexate, azathioprine in
combination of low dose steroids.
- Tend to keep prednisone dose at
around 10 mg or less to avoid risk of
renal crisis.
GI Involvement
Myositis
Pulmonary Involvement

38.  Pericarditis:
- NSAIDs
- Drainage of effusion if
tamponade
 Myocarditis with elevated
CK-MB & troponin
- If CAD is excluded, MRI
and biopsy confirms, then
treatment would generally be
with low dose prednisone (10
mg/day) and cytoxan; nifedipine
may also be helpful.
 Stable disease: no treatment
 Advancing diffuse skin
involvement:
• Methotrexate
• Mycophenolate
• Current trial with Tocilizumab
(Actemra)
• D-penicillamine 125 mg/day.
• Research on various anti-fibrosis
therapies is being performed
(imatinib, Gleevac).
Cardiac Involvement Skin Disease

39.  Scleroderma
• No Raynauds, negative antibodies, seen in IDDM
• Proximal skin thickening (trunk, shoulders, back)
 Scleromyxedema
• Skin thickening/induration on head, neck, arms, trunk
• Monoclonal gammopathy (multiple myeloma/AL amyloid)
• Skin biopsy differentiates.
 Endocrinologic: diabetes and hypothyroid myxedema
• Can be associated with skin induration.
• In diabetes can have sclerodactyly (Diabetic Cheiroarthropathy) - dorsal
• POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin thickening).
 Nephrogenic Systemic fibrosis
• Chronic kidney disease and gadolinium MRI contrast
• Can involve hands and feet.
 Eosinophilic fasciitis:
• Hands and feet are spared, peripheral blood eosinophilia, peau de orange appearance
• Diagnosis is via skin biopsy.
 Graft versus Host disease
• History of bone marrow transplant, no Raynaud’s symptoms.
• Diagnosis is via skin biopsy.
Differential Diagnosis

40. • Medscape & PubMed
• Up To Date
• Curr Opin Rheumatol 23;505-510
• Fischer A; CHEST 2006; 130:976 –981
• Rheum Dis Clin N Am;2003;29:293–313
• Arthritis Rheum 2006;54:3962-3970
• Rheumatology 2009;48:iii32–iii35
• Desai, et al; Curr Opin Rheumatol 2011; 23:545-554
• Steen VD; Rheum Dis Clin N Am 2003;29:315–333
• Hudson M, et al; Medicine 2010;89:976-981
• Bon LV; Curr Opin Rheumatol 2011;23:505–510
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References;